JOURNAL ARTICLE

In vitro activity of anti-leishmanial drugs against Leishmania donovani is host cell dependent

Karin Seifert, Patricia Escobar, Simon L Croft
Journal of Antimicrobial Chemotherapy 2010, 65 (3): 508-11
20089542

OBJECTIVES: To evaluate the in vitro activity of anti-leishmanial drugs against intracellular Leishmania donovani amastigotes in different types of macrophages.

METHODS: Mouse peritoneal macrophages (PEMs), mouse bone marrow-derived macrophages (BMMPhi), human peripheral blood monocyte-derived macrophages (PBM Phi) and differentiated THP-1 cells were infected with L. donovani. Cultures were incubated with sodium stibogluconate, amphotericin B deoxycholate (Fungizone), miltefosine or paromomycin sulphate over six concentrations in 3-fold serial dilutions for 5 days. Analysis was based on percentage inhibition of infected macrophages and EC(50)/EC(90) values estimated using sigmoidal curve-fitting.

RESULTS: The rank order of drug activity was the same in the different macrophage populations: amphotericin B > miltefosine > sodium stibogluconate > paromomycin. However, significant (P < 0.05) differences were observed between populations. Amphotericin B was more active in PEMs and BMM Phi (EC(50) 0.02-0.06 microM) compared with PBM Phi and differentiated THP-1 cells (EC(50) 0.08-0.40 microM) and miltefosine was more active in PBM Phi (EC(50) 0.16-0.74 microM) compared with PEMs and BMM Phi (EC(50) 2.60-7.67 microM). Sodium stibogluconate displayed highest activity in PBM Phi (EC(50) 1.38-1.89 microg Sb(v)/mL), followed by PEMs (EC(50) 21.75-27.79 microg Sb(v)/mL) and BMM Phi and differentiated THP-1 cells (EC(50) 28.96-112.77 microg Sb(v)/mL). Paromomycin showed highest activity in PBM Phi (EC(50) 80.03-104.38 microM) and PEMs (EC(50) 75.42-201.63 microM).

CONCLUSIONS: In vitro activity of anti-leishmanial drugs is host cell dependent. This has implications for: (i) the evaluation of in vitro drug activity; (ii) the evaluation of drug susceptibility of clinical isolates; and (iii) the standardization of anti-leishmanial drug assays.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
20089542
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"